We propose to expand our investigations on the use of the multicellular spheroid tumor model system as a predictive model for some types of drug-radiation interactions. The internal levels of pO2 and pH of various size ranges of spheroids have been defined for normal growth and experimental conditions. We now propose to employ oxygen and pH ultramicroelectrodes to further study and define this model system when the external environment is modified by changes in temperature, pH, pO2 and media composition. In addition we propose to extend our studies on the use of current chemotherapeutic drugs as indirect radiation sensitizers. The model system predicts that Chlorambucil and Mustargen are effective sensitizers in this class. We propose to test each of these in vivo tumor system. Also, several new drugs will be entered into the study of drug-radiation interactions at the cellular level in monolayer and spheroid cell cultures. These drugs will include nitrosoureas (PCNU), anthracenedione and local anaesthetics with each being tested for direct and indirect interactive effects with radiation.